Distinguishing Dementia with Lewy Bodies From Parkinson's Disease Dementia and Alzheimer's Disease: A Geriatric Case Study
Mr. P* is a 71-year-old widowed male resident of an assisted living facility who was recently diagnosed with Parkinson’s disease (PD), depression, and generalized anxiety. Mr. P had no prior history of mental illness. He acknowledged some regular alcohol use as a young man, consisting of drinking three to four alcoholic beverages per day over many years, but denied any alcohol-related blackouts, seizures, or treatment. Recent symptoms of anxiety and depression were attributed to a prolonged grief reaction from the loss of his wife just two years prior to admission. Mr. P is highly educated and was active in the community until the death of his wife. Following her death, Mr. P began to experience a steady progression of his parkinsonian symptoms, including a mild intention tremor, cogwheel rigidity, and prominent bradykinesia. Functional decline eventually led him to the assisted living unit, where he required increasing assistance with bathing, dressing, and medication management. He was referred to a neurologist for evaluation of his worsening PD and was started on a low dose of pramipexole.
Over time, assisted living staff observed him to be engaged in heated discussions while sitting alone in his room. Mr. P became more disturbed by images of people and animals he saw in his room, but he was often content to interact with the hallucinatory figures. On one occasion, he expressed concern that someone in the assisted living facility was attempting to murder him. He also described feeling as though he was a character in a play, and that nothing around him was real. Staff expressed concern that Mr. P was increasingly volatile, losing his temper easily for unclear reasons, and becoming confused at various times during the day and night. On medical evaluation, Mr. P was found to be mildly febrile, diaphoretic, and with persistent parkinsonian symptoms. Laboratory studies suggested dehydration and mild leukocytosis. He was transferred to a local community hospital where a chest x-ray revealed a small left lower lobe infiltrate. Mr. P was started on intravenous antibiotics and fluids with minimal difficulty.
A psychiatric consultation was requested to assess Mr. P’s increasing paranoia about the intentions of other patients and the small animals he noticed running through the ward. Pramipexole was discontinued, and a neurological consultant suggested that further trials of dopaminergic agonists be held until his psychiatric condition was more clearly defined and stabilized. Routine laboratory studies were all within normal limits, and a brain magnetic resonance imaging scan did not reveal any evidence for vascular disease, tumor, or cortical atrophy. Mr. P was started on quetiapine 12.5 mg at bedtime, and this dose was tolerated well. The dose was increased gradually in increments of 12.5 to 25 mg per day, until he reached a dose of 100 mg twice daily. Although he had some difficulty tolerating the sedating side effects, Mr. P was notably more organized in his thinking, less anxious during the afternoon, and markedly less paranoid about other patients harming him; however, his mobility was notably worse on quetiapine, and he required a walker to reduce the risk of falls. Mr. P was also started on donepezil 5 mg at nighttime.
* Details of this case have been altered to protect the identity of this patient.
Recognizing dementia with Lewy bodies (DLB) as a distinct diagnostic entity is often a challenge for geriatricians because its presentation and course commonly overlap with other disease states. Some of the confusion is due to the understanding that DLB may co-occur with Alzheimer’s disease (AD) or with PD, or exist along a continuum of degenerative diseases. Identifying clinical distinctions between DLB, AD, and PD may assist providers in their management of behavioral and functional decline. Future clinical trials will increasingly focus on the differences in response to various treatments such as cognitive enhancers. This case study illustrates some of the complexities in identifying a pattern of disease progression and various symptoms that may occur with DLB, PD, and AD.
Features of Dementia with Lewy Bodies
The case of Mr. P demonstrates many of the core features of DLB, and raises questions regarding the overlap of this disease with other clinical diagnoses such as Parkinson’s disease dementia (PDD) and AD. The central shared feature of each of these degenerative diseases is the finding of progressive cognitive decline. Dementia with Lewy bodies is also characterized by notable fluctuations in consciousness, alertness, and cognition that may easily be attributed to other types of dementia or delirium.1 The timing of these fluctuating states is quite variable in DLB, in contrast to the diurnal patterns of confusion often found in delirium that may be termed “sundowning” or transient nocturnal delirium. As frequently occurs in older adults, the presentation of Mr. P was also complicated by delirium, and the pre-existing attentional fluctuations worsened to the point where he was found to be acutely more confused and volatile.
A second commonly described symptom of DLB is that of complex and well-formed visual hallucinations.1 Many patients with DLB describe animate hallucinations such as little people, animals, or children; however, these details are not specific to DLB, and the findings of recurrent visual hallucinations are generally similar in DLB and PDD.2 Not surprisingly, there is some controversy over the assertion that visual hallucinations and cognitive fluctuations characterize DLB with sufficient specificity to represent true distinctive criteria for this disease entity.3
A third core finding of DLB involves the spontaneous emergence of parkinsonian motor signs.1 Bradykinesia and rigidity are fairly typical presenting symptoms, and the tremor is greater with intention than resting. Gait, balance, and posture are also frequently affected. This instability, combined with autonomic dysfunction, contributes to injuries from repeated and unexplained falls commonly found in patients with DLB. In addition, parkinsonism induced by psychotropic medications is highly exacerbated in patients with DLB who are overly sensitive to the dopamine blockade of antipsychotic medications.
Differentiating Between Dementia with Lewy Bodies, Parkinson’s Disease Dementia, and Alzheimer’s Disease
Making distinctions between DLB, PDD, and AD based on clinical criteria such as fluctuations in attention, hallucinations, parkinsonism, and cognitive decline can be exceedingly difficult as there is a fair amount of overlap among each of these disease entities (Table). However, there is probably greater similarity between patients with DLB and PDD, as compared to the more typical presentation of patients diagnosed with AD. For instance, there is no major difference between the fluctuation of attention found in DLB and that found in PDD.4 In addition, visual hallucinations occur with similar frequency among patients with DLB and PDD, and patients with either disorder may also suffer from increasing hallucinations when taking dopaminergic medications,5 as may have occurred in the case of Mr. P. Alternatively, patients with DLB will usually experience hallucinations earlier in the course of the disease as compared to patients with AD.6
In DLB, cognitive decline generally begins within one year of the onset of extrapyramidal motor symptoms,1 but this finding is still considered variable and arbitrary. There is no current evidence to validate the timing of cognitive impairment as a formal criterion to distinguish DLB and PDD. It is widely believed, though, that the emergence of cognitive impairment in PDD usually occurs after more than two years following the onset of motor symptoms.3 The idea that dementia developing in less than two years from the onset of motor symptoms would be defined as Lewy body disease suggests that these are diagnostic entities lying upon a continuum differentiated merely by degree and pathophysiologic circumstance. To complicate matters further, there is a subset of patients with DLB—perhaps as many as 25%—for whom there is little or no parkinsonism on exam,7 adding to the challenge for any clinician trying to make an accurate diagnosis. Estimates of the proportion of patients with PD who will eventually meet criteria for dementia range from 40% up to 78%, with the upper-range figure reflecting studies of patients followed longitudinally over a longer duration of time.8 However, unlike the findings in PD, cognitive decline occurs in all patients diagnosed with DLB.
There is a significant overlap between the neuropathology of AD and that of DLB. Both Lewy bodies and beta-amyloid plaques are found in some abundance in patients with DLB and AD, suggesting a shared mechanism of dysregulated protein metabolism;3 however, the cognitive deterioration of DLB may be distinct from findings in the typical AD presentation. Patients with DLB tend to have more pronounced deficits in attentional, executive, and visuospatial domains, with relative preservation of short-term memory function. In later stages of either disease, these distinctions are less significant or helpful in making an accurate diagnosis. In addition to cognitive deficits, there are also differences in the nature and degree of functional impairments resulting from AD and DLB. Due to the characteristically more pervasive and severe extrapyramidal symptoms found in DLB as compared to AD, clinicians might expect significantly greater functional difficulties in their patients’ ability to eat properly, ambulate, transfer, bathe, and toilet independently.9
Treatment Options for Dementia with Lewy Bodies
Managing behavioral disturbances and mood lability in patients with DLB often requires a delicate titration of mood stabilizers to either augment or replace antipsychotic medications. Although no controlled studies exist to date, many clinicians effectively utilize mood stabilizers such as valproic acid to address agitated and aggressive behaviors. For patients with predominant psychotic symptoms or behavioral disturbances that are not responsive to mood stabilizers alone, antipsychotic medications must be initiated at very low doses. Patients with DLB are more likely to tolerate antipsychotic medications such as quetiapine or clozapine that produce relatively transient or lower levels of dopamine blockade and are less likely to cause clinically debilitating extrapyramidal symptoms.10 One open-label study of nine patients diagnosed with DLB showed marked improvement in psychotic symptoms after receiving quetiapine in doses ranging from 25 mg to 300 mg per day.11 None of these patients showed any worsening in motor symptoms, and more than half actually demonstrated some improvement in motor function.11
Low doses of sedating antidepressant medications such as trazodone are often used for their soporific effects. While this strategy is often effective, clinicians must always take caution monitoring for any increased risk of orthostasis, unsteady gait, and falls. Another commonly employed pharmacological treatment, as noted in the case of Mr. P, involves the use of dopaminergic agonists to relieve worsening parkinsonism. However, the potential risks of worsening agitation, visual hallucinations, and psychosis from the use of antiparkinsonian medications may outweigh the minimal benefits offered by these agents. Though it has been suggested that response to carbidopa/levodopa could provide some evidence supporting the diagnosis of PD, this was not done in Mr. P’s case. A trial of carbidopa/levodopa was considered after his acute infection had resolved, but the prescribing clinician remained concerned that this medication would potentially worsen pre-existing psychotic symptoms.
Patients with DLB have a cholinergic deficit exceeding that found in AD.12,13 Thus, clinicians should strongly consider prescribing cholinesterase inhibitors for patients with DLB. There is one double-blind, placebo-controlled study available suggesting that a cholinesterase inhibitor, rivastigmine, improved neuropsychiatric symptoms in patients with DLB.14 Symptoms of anxiety, apathy, and disinhibition were most significantly improved for subjects taking rivastigmine. There was also a trend toward improvement in cognition and global function.14 Two smaller studies using the cholinesterase inhibitor donepezil showed a reduction of hallucinations in DLB,15,16 suggesting that use of these medications may decrease reliance upon antipsychotic medications and potential exposure to other secondary side effects.
A crucial aspect of managing DLB involves educating family members and caregivers about the expected course of this disease. Simple interventions such as providing social support and accessible day programs for the affected family member may help them prepare for the rapid changes that may occur as this disease progresses. Legal consultation may also be important as decision-making capacities begin to decline. Behavioral treatment strategies utilizing appropriate milieu, structured activities, sensory stimulation, exercise, music, art, and pet therapies offer alternative approaches to minimize behavioral disturbances and may reduce the need for pharmacotherapy with its attendant side effects. One recent review of these treatment approaches suggests that behavioral management therapies and caregiver/staff education may have lasting effectiveness for managing the neuropsychiatric symptoms of dementia.17 The greatest demands fall upon caregivers to manage the daily safety and routine care of individuals with DLB and related degenerative diseases; however, it is primarily the responsibility of healthcare providers to recognize specific aspects of this disease process and reduce the growing burden of disease from untreated psychosis, behavioral disturbances, and functional decline.
The case described herein highlights some of the challenges in distinguishing DLB from other degenerative diseases such as AD and PD. The overlap of clinical signs and symptoms, combined with the paucity of specific diagnostic indicators or measures, leaves treatment providers to rely upon their clinical skills to examine these patients closely over time. Learning more about the disease onset and progression, gathering further details from caregivers and family, and evaluating the response to psychopharmacological interventions can assist in making a more accurate diagnosis. Future research may allow for more specific and sensitive indicators to help differentiate DLB from other disease entities. This distinction will be more pressing as new clinical investigations suggest that specific treatments for DLB may be more efficacious for this disease process, and may hopefully reduce the burden for patients and caregivers alike.
Outcome of the Case Patient
Neuropsychological testing was obtained and revealed moderate impairment in executive function, spontaneous recall memory, and visuoconstruction. Mr. P was slow in his mentation and function, demonstrating easy fatigue, with difficulty initiating responses to questions. The evaluator concluded that he had an early form of dementia, but was unable to specify if the findings were consistent with PDD, alcohol dependence/abuse in the past, or some other neurodegenerative process. Mr. P was eventually discharged back to his assisted living facility with a plan for close follow-up by a geriatric psychiatrist and clinical nurse specialist. Mr. P continued to take both quetiapine and donepezil, and his behavior and psychotic symptoms remained in good control at the time of follow-up evaluation.
The authors report no relevant financial relationships.